Document Detail

64-Slice CT angiography of the abdominal aorta and abdominal arteries: comparison of the diagnostic efficacy of iobitridol 350 mgI/ml versus iomeprol 400 mgI/ml in a prospective, randomised, double-blind multi-centre trial.
Jump to Full Text
MedLine Citation:
PMID:  19789884     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: The purpose of this study was to assess the influence of iodine concentration on diagnostic efficacy in multi-detector-row computed tomography (MDCT) angiography of the abdominal aorta and abdominal arteries. METHODS: IRB approval and informed consent were obtained. In this double-blind trial, patients were randomised to undergo MDCT angiography of the abdominal arteries during administration of iobitridol (350 mgI/ml) or iomeprol (400 mgI/ml). Each centre applied its own technique for delivery of contrast medium, regardless of iodine concentration. Diagnostic efficacy, image quality, visualisation of the arterial wall and arterial enhancement were evaluated. A total of 153 patients received iobitridol and 154 received iomeprol. RESULTS: The ability to reach a diagnosis was "satisfactory" to "totally satisfactory" in 152 (99.3%) and 153 (99.4%) patients respectively. Image quality was rated as being "good" to "excellent" in 94.7 and 94.8% segments respectively. Similar results were observed for image quality of arterial walls (84.3 vs. 83.2%). The mean relative changes in arterial enhancement between baseline and arterial phase images showed no statistically significant differences. CONCLUSION: This study demonstrated the non-inferiority of the 350 versus 400 mgI/ml iodine concentration, in terms of diagnostic efficacy, in abdominal MDCT angiography. It also confirmed the high robustness and reliability of this technique across multi-national practices.
Authors:
Christian Loewe; Christoph R Becker; Riccardo Berletti; Carlo Alberto Cametti; Jerome Caudron; Walter Coudyzer; Johan De Mey; Massimo Favat; Jean-François Heautot; Sam Heye; Markus Hittinger; Antoine Larralde; Jean-Pierre Lestrat; Roberto Marangoni; Koenraad Nieboer; Peter Reimer; Martin Schwarz; Melanie Schernthaner; Johannes Lammer
Related Documents :
2957514 - Graft reconstruction to treat disease of the abdominal aorta in patients with colostomi...
24570504 - Early type ii endoleak repair after endovascular therapy in behcet's disease.
10525864 - Diagnosis and treatment of expanding haematoma of the lateral abdominal wall after blun...
835984 - Marlex mesh wrapping of abdominal aortic aneurysm.
23665784 - Coronary chronic total occlusions and percutaneous coronary intervention.
24826254 - Subacute staphylococcus epidermidis bacterial endocarditis complicated by mitral-aortic...
Publication Detail:
Type:  Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2009-09-30
Journal Detail:
Title:  European radiology     Volume:  20     ISSN:  1432-1084     ISO Abbreviation:  Eur Radiol     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-16     Completed Date:  2010-05-18     Revised Date:  2010-09-28    
Medline Journal Info:
Nlm Unique ID:  9114774     Medline TA:  Eur Radiol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  572-83     Citation Subset:  IM    
Affiliation:
Section of Cardiovascular and Interventional Radiology, Department of Radiology, Medical University Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. christian.loewe@meduniwien.ac.at
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Aged
Angiography / methods*
Aorta, Abdominal / radiography*
Contrast Media
Dose-Response Relationship, Drug
Double-Blind Method
Europe
Female
Humans
Image Enhancement / methods*
Iohexol / administration & dosage,  analogs & derivatives*
Iopamidol / administration & dosage,  analogs & derivatives*
Male
Prospective Studies
Reproducibility of Results
Sensitivity and Specificity
Tomography, X-Ray Computed / methods*
Chemical
Reg. No./Substance:
0/Contrast Media; 0/iobitridol; 62883-00-5/Iopamidol; 66108-95-0/Iohexol; 78649-41-9/iomeprol
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Eur Radiol
ISSN: 0938-7994
ISSN: 1432-1084
Publisher: Springer-Verlag, Berlin/Heidelberg
Article Information
Download PDF
? The Author(s) 2009
Received Day: 27 Month: 3 Year: 2009
Accepted Day: 13 Month: 8 Year: 2009
Electronic publication date: Day: 30 Month: 9 Year: 2009
pmc-release publication date: Day: 30 Month: 9 Year: 2009
Print publication date: Month: 3 Year: 2010
Volume: 20 Issue: 3
First Page: 572 Last Page: 583
ID: 2822224
PubMed Id: 19789884
Publisher Id: 1600
DOI: 10.1007/s00330-009-1600-6

64-Slice CT angiography of the abdominal aorta and abdominal arteries: comparison of the diagnostic efficacy of iobitridol 350?mgI/ml versus iomeprol 400?mgI/ml in a prospective, randomised, double-blind multi-centre trial
Christian Loewe1 Address: christian.loewe@meduniwien.ac.at
Christoph R. Becker2
Riccardo Berletti3
Carlo Alberto Cametti4
Jerome Caudron5
Walter Coudyzer6
Johan De Mey7
Massimo Favat3
Jean-Fran?ois Heautot8
Sam Heye6
Markus Hittinger2
Antoine Larralde8
Jean-Pierre Lestrat5
Roberto Marangoni4
Koenraad Nieboer7
Peter Reimer9
Martin Schwarz9
Melanie Schernthaner1
Johannes Lammer1
1Section of Cardiovascular and Interventional Radiology, Department of Radiology, Medical University Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria
2Department of Clinical Radiology, University Hospital Grosshadern, Munich, Germany
3Department of Radiology, Belluno Civil Hospital, Belluno, Italy
4Department of Radiology, ASL TO2 Ospedale San G. Bosco, Torino, Italy
5Department of Radiology, University Hospital of Rouen, Rouen, France
6Department of Radiology, UZ Leuven, Leuven, Belgium
7Department of Radiology, UZ Brussel, Brussels, Belgium
8Department of Radiology, Pontchaillou Hospital, Rennes, France
9Department of Radiology, St?dt. Klinikum Karlsruhe, Karlsruhe, Germany

Introduction

Multi-detector-row computed tomography (MDCT) has been established as the method of choice for the diagnosis, treatment planning and follow-up of most diseases of the abdominal arteries, including the renal [1?4] and visceral arteries [5, 6] and the aorta [7?9]. In these anatomical regions, diagnostic invasive arteriography (digital subtraction angiography, DSA) has steadily been replaced over the past few years by non-invasive CT angiography and, in some cases, by non-invasive magnetic resonance (MR) angiography [10?12].

However, the broad use of MDCT in the clinical routine, as well as the choice of contrast agent and administration technique thereof, still remains controversial. Many authors have shown that the enhancement of the abdominal arteries is directly correlated to the amount of iodine (not contrast agent) per second [5, 13], also known as the ?iodine flux?. The higher the iodine flux, the higher the density will be within the region of interest. On the other hand, increasing the total amount of iodine could raise safety issues such as concern of contrast-induced nephropathy (CIN) in at-risk patients. Because a lower total amount of iodine lowers the risk of CIN [14?16], protocols for CT angiography should always find a compromise between the required contrast enhancement and the amount of iodine injected.

Although many papers have been published about preferred methods of administering contrast medium, some questions remain unanswered. It is still unclear as to what degree of vascular opacification (in Hounsfield units, HU) is really necessary to obtain diagnostic images; in other words, does higher density, which can possibly be reached with more highly concentrated agents and higher iodine flux, really further improve diagnostic accuracy? Finally, even injection parameters still need to be standardised. Fleischmann and Hittmair [5, 17?19] have shown the advantages of using a biphasic contrast injection, calculated individually for every patient, in CT angiography of the abdominal aorta. However, these studies were performed on single-slice systems with long acquisition times. With fast imaging, using 64-slice CT systems, it seems that injection protocols could be made much easier, and the benefit of a contrast medium with higher iodine concentrations could be of great importance. In addition, optimum injection rate, optimum iodine concentration and optimum total volume of contrast medium for abdominal CT angiography still need to be determined.

In the present trial, patients were investigated during the injection of two different contrast agents with different iodine concentrations (350 vs. 400?mgI/ml). In contrast to some recently published papers [20], where patients were examined with different iodine concentrations but constant iodine flux rates, the injection protocol in the present study was not adapted to the iodine concentration of the agent used. In addition, the various centres participating in the present trial were to use their own injection protocols. A lack of relevant differences in diagnostic efficacy, image quality and arterial contrast enhancement among the centres will emphasise how stable and easy to perform abdominal CT angiography is in clinical settings if state-of-the-art equipment is used.

The aim of this prospective, randomised study was, therefore, to assess the influence of iodine concentration on diagnostic efficacy in CT angiography of the abdominal and visceral arteries.


Materials and methods
Study design and patient enrolment conditions

This study was a non-inferiority, randomised, double-blind, prospective, multi-centre trial in patients referred for CT angiography of the abdominal aorta and its branches. Nine European centres were involved in this trial between August 2006 and February 2008. The study protocol was approved by the local Ethics Committees and Competent Authorities.

As this study was designed to reflect the conditions of daily routine, patients were included in a consecutive manner, regardless of the indication for the examination. Patients between 18 and 85 years of age were eligible for study participation. A history of previous (open surgical or endovascular) vascular treatment in the abdomen was not an exclusion criterion. Patients with haemodynamic instability, non-compensated heart failure or hypertension (systolic blood pressure ?180?mmHg or diastolic blood pressure ?110?mmHg) were not included. In addition, patients with severe renal insufficiency [defined as estimated creatinine clearance (Cockroft and Gault) below 30?ml/min], treatment with diuretics or biguanides within 48?h before CT angiography, known thyrotoxicosis or a history of hypersensitivity to iodinated contrast agents were not included. Breast-feeding or pregnant women were also excluded from participation in this trial.

After providing written, informed consent, patients were randomised into two examination groups according to a randomisation list stratified on centres and balanced every four patients. Patients in the first group were to undergo the abdominal CT angiography with injection of iobitridol 350?mgI/ml (Xenetix?, Guerbet, Roissy, France); patients in the second group were to be examined by means of CT angiography with injection of iomeprol 400?mgI/ml (Iomeron?, Bracco, Italy).

CT angiography

All patients included in the present evaluation were scheduled to undergo CT angiography of the abdominal aorta and abdominal arteries. All examinations were performed on 64-slice single-source CT systems (two Siemens SOMATOM Sensation, four General Electrics LightSpeed VCT, two Philips Brillance 64), and on a dual-source Siemens SOMATOM Definition used as a single-source.

Imaging protocol

To allow direct measurement of abdominal arterial enhancement, the study examination consisted of two steps including unenhanced imaging of the abdomen followed by abdominal CT angiography during the arterial first pass. If clinically indicated, additional venous or late-phase imaging could also be performed outside the study protocol.

Study centres were advised to use their own routinely used imaging protocol for abdominal CT angiography. Only a maximum allowed volume of 150?ml was predefined by the study protocol; all additional parameters, including injection rate and volume, were to be determined by the investigators. No compensations based on the different iodine concentrations of the contrast agents being compared were performed, as the investigators were blinded to both products. Thus, iodine flux, meaning the iodine administration per unit of time, was lower in the group receiving iobitridol than in the group receiving iomeprol.

MDCT angiography was performed using automatic bolus detection software (Smart Prep?, Care Bolus?, or equivalent) to identify peak contrast enhancement and to launch the acquisition. The whole abdomino-iliac system from above the suprarenal aorta to the femoral bifurcation was to be covered in one imaging procedure.

As the study centres were asked to use their own clinically established examination protocols, the kilovoltage (kV) and milliampere seconds (mAs) values differed among centres as did the average duration of the examination.

Injection of contrast medium

To ensure contrast agent administration in double-blind conditions, allocation of patients to one of the two groups (iobitridol or iomeprol group) and the preparation of the contrast agent, pump and injection were performed by a radiographer or nurse who was not involved in the subsequent evaluation. The contrast agent used was not identified on the images to allow blinded reading.

Patient follow-up

Clinical safety monitoring started at inclusion and lasted until 1?h after the end of the examination.

Evaluation

All CT images were assessed on-site by one local investigator at each participating hospital. The investigator was blinded to the contrast material used for each patient.

Diagnostic efficacy

Diagnostic efficacy (primary endpoint) of the CT examination was defined as the level of available information for diagnosis provided by the MDCT examination. Readers rated the diagnostic efficacy of the CT angiographies using a four-point scale ranging from 0, i.e. not satisfactory (?not providing enough information = complementary examination recommended?), to 3, i.e. totally satisfactory (?providing the expected information?), with level 1 indicating not satisfactory (?not providing all the expected information = could need a complementary examination?) and 2 representing satisfactory (?providing sufficient information?). The primary endpoint was calculated within both product groups by a cumulative proportion of those patients who presented with satisfactory (level 2) to totally satisfactory (level 3) images, and then the two product groups were compared.

Image quality according to vascular territories

As one of the secondary study criteria, the quality of images was evaluated in 16 pre-specified segments from the aorto-ilio-femoral axis: the suprarenal, the juxtarenal and the infrarenal aorta; the coeliac axis and its branches; the superior and inferior mesenteric artery; the right and left renal artery; the right and left common and external iliac artery; the right and left hypogastric artery; and the right and left common femoral artery.

In all of these 16 arterial segments, image quality was rated according to a four-point scale, i.e. 0 (null), 1 (poor), 2 (good) and 3 (excellent). If the segment was not delineated by the field of view (FOV), it was counted as ?not applicable?. In the case of a 0 rating or poor quality, the reason for insufficient quality was indicated. This endpoint was calculated within both product groups by a cumulative proportion of vascular segments that presented with good (2) and excellent (3) image quality, and then the two product groups were compared.

Quality of vascular wall visualisation

Additionally, the quality of arterial wall visualisation within the 16 segments defined above was assessed. This evaluation was focused on changes within the vascular wall, including internal deposition of thrombotic material or inflammatory reaction, if present, and used the four-point scale mentioned above. In the case of a 0 rating or poor quality, the reason for this insufficient quality was indicated. This criterion was calculated within both product groups by a cumulative proportion of vascular wall segments that displayed with good (2) and excellent (3) image quality, and then the two groups were compared.

Quantification of arterial enhancement

As an additional endpoint, arterial enhancement was measured in eight predefined areas, including the suprarenal and the infrarenal aorta, the right and left renal artery, the right and left common iliac artery, and the right and left common femoral artery, and compared between the two groups. For measurement purposes, regions of interest (ROIs) were defined on unenhanced as well as enhanced images in the same table position (Fig.?1). According to the study protocol, the circumference of the ROI should not extend beyond the internal limit of the arterial wall. For the aorta, the ROI was to be located in the middle of the vessel and for its branches in the first 2?cm (Fig.?1). The two groups? average absolute and relative enhancements were compared.

Clinical safety

In addition to the efficacy evaluation, the safety profile of both contrast agents was investigated, and any event, starting from inclusion until the end of the follow-up period (1?h after the end of CT angiography), was collected and reported.

Statistical evaluation

Assuming that in the iobitridol group and the iomeprol group at least 90% of patients would provide CT images with a satisfactory to totally satisfactory level of diagnostic information [21, 22], non-inferiority was defined as a difference between the two products (? = Piobitridol - Piomeprol) that was statistically higher than the clinical non-inferiority limit set at ?0?=??10% in the study (maximum negative difference allowed between iobitridol and iomeprol). The study was to be demonstrative if the 95% confidence interval of the difference excluded the ?0?=??10% clinical non-inferiority limit.

Before starting the trial, the sample size of the study (310 patients) was calculated so that the non-inferiority of iobitridol (350?mgI/ml) in providing the same level of diagnostic information as iomeprol (400?mgI/ml) could be statistically demonstrated with 80% power and 5% type-one error.

Confidence intervals and associated P values were computed for the estimated parameters based on the asymptotic normality of maximum likelihood estimators and using the Wald ?2 statistics in the SAS Genmod procedure. This procedure computes a generalised linear model, particularly suitable for adjusting on covariates and modelling clustered data (assessments at segment level nested in patients in the present study). In addition, the exact confidence interval and exact P value were also computed for the primary endpoint using StatXact software (Cytel Statistical Software & Services).


Results
Baseline characteristics and examination protocol

In total, 310 patients (247 men and 63 women; mean age: 66.5 years old) referred for CT angiography of the abdominal aorta and/or the abdominal arteries were enrolled in this trial. The baseline characteristics of the study population were well balanced between groups (Table?1).

Indications for CT included post-surgical follow-up (56.5%), pre-therapeutic assessment (36.1%) or other indications (7.4%), such as staging of lymphomas or gastric carcinomas. At the time of examination, 92 patients had various clinical symptoms, including hypertension (11.9%), limb ischaemia (10.7%), abdominal pain (9.4%) or other (5.5%). Moreover, 129 patients had a history of endovascular and/or surgical treatment of abdominal arteries (66 in the iobitridol group and 63 in the iomeprol group).

Of the 310 patients included, 154 were randomly assigned into the iobitridol group, and 156 into the iomeprol group, and only 1 patient was not injected for technical reasons.

Most of the centres (n?=?6) performed the CT angiographies at a fixed tube voltage of 120?kV; the others at either 100 or 120?kV. The mean mAs used was 319.0 (range 63?896?mAs). No differences could be noticed between groups for those two parameters.

As shown in Table?2, four centres (accounting for 149 patients or 48% overall) injected the same fixed volume of contrast material at a fixed injection rate, regardless of the patient?s weight or indication for the examination. The other five centres adjusted the injection protocol to the patient?s condition. Between 63?and 140?ml of contrast agent were injected at a rate of 2.5?6?ml/s. On average, patients received 101.0?ml in the iobitridol group and 101.5?ml in the iomeprol group corresponding respectively to 35.4 and 40.6?g iodine, indicating that there was no additional volume injected to balance the lack of iodine in the iobitridol group.

The average duration of the examination (from time of injection to the end of CT) ranged from less than 1?min up to 14?min (mean of all centres: 1?min 22?s; standard deviation: 1?min 37?s).

Overall diagnostic efficacy

Of the 310 patients included, 3 were excluded from the efficacy analysis for technical reasons (1 in the iobitridol group and 2 in the iomeprol group).

Of the 307 patients available for further evaluation, diagnostic efficacy was rated satisfactory or totally satisfactory in 152 patients (99.3%) of the iobitridol group and in 153 patients (99.4%) of the iomeprol group. Non-inferiority was statistically demonstrated between the two products (exact 95% confidence interval [?2.98%; 3.01%] excluding the ?10% clinical non-inferiority limit; Table?3).

Non-inferiority still holds if the maximum grade (totally satisfactory) of both products is considered and compared, as the exact 95% CI (?4.8%; 3.2%) still excludes the ?10% clinical non-inferiority limit (Table?3).

The two examinations which failed to provide sufficient diagnostic information were performed in patients who had a history of endovascular and/or surgical treatment of abdominal arteries.

Image quality according to vascular territories

Of the 2,448 vascular segments assessed in the iobitridol group and 2,464 in the iomeprol group, 2,319 (94.7%) and 2,336 (94.8%) were rated as being of ?good? to ?excellent? image quality respectively. Differences between the two groups were statistically not significant (P?=?0.5769), and 95% confidence intervals were small enough to conclude the equivalence of both contrast agents (Table?4; Fig.?2).

Eighty-three segments were not assessable (out of the FOV, not applicable).

Quality of vascular wall visualisation

The quality of vascular wall visualisation was assessed in 2,448 segments in the iobitridol group and in 2,464 in the iomeprol group. It was rated good to excellent in 2,064 (84.3%) and 2,049 (83.2%) segments respectively. The differences between the two groups in this regard were statistically not significant (P?=?0.8316), and 95% confidence intervals were small enough to conclude the equivalence of the two contrast agents (asymptotic 95% CI [?6.33%; 7.87%]) (Table?5).

Quantification of arterial enhancement

As expected, there was no difference in the mean baseline values between the two groups (40.0?HU in the iobitridol group; 40.8?HU in the iomeprol group). After contrast injection, mean arterial enhancement was 320.4?HU (SD, 93.54; range, 42?638) in the iobitridol group and 353.6?HU (SD, 95.45; range, 25?770) in the iomeprol group. The enhancement variation statistically differed between groups when considering the absolute variation (P?=?0.0014; 95% CI [?53.47; ?12.85]). Comparing the relative changes from baseline to arterial phase, no statistical difference was observed (P?=?0.0673; 95% CI [?1.53; 0.053]) (Table?6).

Safety

Three patients reported a total of five non-serious adverse events, all occurring after contrast agent injection (diarrhoea, pain, neck rash and swelling in the iobitridol group; nausea in the iomeprol group). Two adverse events (neck rash and diarrhoea) experienced by the same patient were reported after the safety follow-up time required (9 and 33?h after the injection of the contrast agent respectively). All the adverse events had a favourable outcome, and relationship to the contrast agent was assumed for three of them (nausea, rash in neck and diarrhoea).


Discussion

Although non-invasive MDCT angiography has become the method of choice for most indications involving the abdominal and visceral arteries, no general contrast injection protocol has been established to date [13]. A number of papers have evaluated the influence of different parameters for contrast administration, including iodine concentration, total volume of contrast, injection rate, and other factors [20, 23?25], on arterial and/or parenchymal enhancement [13], but very limited general recommendations on optimised parameters could be gleaned from these publications. The very simple and basic relation, expressed as ?the higher the iodine application per unit of time, the higher the enhancement? seems to be an established general rule for MDCT angiography following most of these publications [13, 19]. However, the question of whether this higher iodine flux should be reached by using a higher iodine concentration or a higher injection flow remains unclear, despite the number of studies recently published in this field [20, 25]. A study conducted by Awai et al. [24] concluded that arterial enhancement could be improved by increasing the iodine concentration of the contrast agent. In this study, the injection rate was the same for both products (0.56?ml/s/kg). Despite the fact that the results of the latter study are concordant with the study results reported by Bae et al. [26], it is apparently still unclear whether a higher concentration of iodine is really beneficial or not in abdominal MDCT angiography, as an additional study by Awai et al. [27] reported that faster injection (4?ml/s) of a lower-concentration agent (300?mgI/ml) led to greater enhancement compared with a slower injection (3.6?ml/s) of a higher-concentration agent (350?mgI/ml).

In fact, from a clinical point of view, the question of how to reach the amount of iodine per time needed for diagnostic images is of limited interest; on the other hand, the question of how much iodine per unit of time is really needed for abdominal MDCT angiography seems to be of greater relevance. Surprisingly, very few recommendations about the minimum iodine flux and minimum total amount of iodine necessary for abdominal CT angiography of sufficient image quality and diagnostic confidence have been published to date [13]. Roos and co-authors have shown that an iodine concentration of at least 300?mgI/ml should be recommended [28]. Ho et al. have shown that the volume of contrast medium can be reduced to a mean quantity of 107?ml (300?mgI/ml) in abdominal aortic CT angiography for aortic aneurysms without a significant decrease in aortic attenuation [29].

From a patient?s point of view, reducing the amount of iodine as much as possible would help to avoid CIN in patients at risk, as the probability of CIN is mainly determined by the amount of iodine delivered to patients [14, 16].

In the present study, two contrast agents (different with regard to their iodine concentration - iobitridol 350?mgI/ml vs. iomeprol 400?mgI/ml) were compared in a large population. The aim of this study was expressly not to test whether a higher-concentration contrast agent is better for arterial enhancement, as published previously in many other papers [20, 24, 25], but to demonstrate that the total amount of iodine can be reduced by more than 12% without significant disadvantages for diagnostic efficacy, image quality, or attenuation of MDCT angiography.

The present study statistically demonstrates the non-inferiority of the 350?mgI/ml iodine concentration vs. 400?mgI/ml in terms of diagnostic efficacy, confirming that a lower total amount of iodine and a reduced iodine flux for abdominal CT angiography does not yield inferior diagnostic contribution results. Moreover, in a per-patient, as well as in the more detailed per-segment evaluation, no significant differences between the two groups were found with regard to image quality (vessels and vascular walls levels) and relative arterial enhancement, emphasising the equality of the contrast agents injected for abdominal MDCT angiography.

The selected study protocol, in which no adaptation of injection parameters to the iodine rate led to different iodine fluxes and a broad range of iodine doses being used (from 24.5 to 56?g, i.e. more than 100%), and the very large number of examinations rated as being of good or almost excellent quality in both groups, exemplifies the limited influence of high iodine concentration and iodine flux on diagnostic efficacy and image quality of ultra-fast MDCT angiography using state-of-the-art 64-slice or dual-source systems (used as single source).

A comparison of these findings with those of previously published studies is difficult, as most of the other comparisons between two iodine concentrations have been performed with a constant iodine flux [20, 24, 25]. The results presented herein are in contradiction to the reports, for example, by Awai [24]. One reason for this difference could be the faster system used in the present study. Performance of a shorter imaging procedure, which is initiated slightly later, could lead to a lesser influence of higher iodine concentrations with regard to image quality.

These findings allow two major conclusions and recommendations to be made for the future development of injection protocols in abdominal MDCT angiography. Firstly, the role played by contrast material selection seems to be limited. Secondly, regarding the distribution of total iodine volumes used by the various investigators in the present study, there seems to be a general trend towards using a larger contrast dose than necessary to obtain images of good or almost excellent quality and high diagnostic efficacy. Additionally, other parameters become more important in the case of ultrafast CT angiographies. Reducing the total amount of contrast to a minimum, optimizing timing of contrast injection and CT scanning, and adapting to the extremely short examination times are mandatory to ensure diagnostic images. Thus, the data published herein should lead us to revise the examination protocols used for abdominal MDCT angiography with the clearly defined purpose of reducing the total amount of iodine. This will help to reduce the potential for the development of CIN in patients at risk.

This study is not free of limitations. First, no correlation with a reference standard was performed. However, as the aim of the study was to assess the diagnostic efficacy, image quality and contrast enhancement, rather than the sensitivity and specificity values in the detection of a dedicated pathological condition, the lack of difference between the two groups seems to be reliable even without a reference standard. As MDCT angiography is now well-established as the method of choice for the diagnosis of most of the different arterial pathological conditions in the abdomen [4], it would have been difficult to examine all included patients with an additional intra-arterial DSA for the purposes of our study.

Another limitation is that only two different iodine concentrations were used with a limited difference in iodine concentration. It would be of great interest to know the exact concentration at which no relevant difference could be observed, in other words, to assess the minimum iodine volume the injection could be reduced to without sacrificing diagnostic efficacy and image quality. Finally, a limitation of this study could be inherent in the different injection protocols; the relevant potential confounding factors (injection rate, volume injected, iodine flux, stent presence, imaging parameters and clinical indication for CT) were well-balanced between both groups and had no statistical impact on the difference between the two products, leading us to consider that the influence of iodine concentration has been addressed.

In conclusion, the present study demonstrates the limited influence of iodine concentration in the range between 350 and 400?mgI/ml on diagnostic efficacy and image quality in abdominal MDCT angiography with 64-slice and dual-source systems (used as single source), and the lack of additional benefit with the use of highly concentrated agents for this purpose. Furthermore, we showed that more iodine than necessary is typically injected into patients. In times of ultrafast CT scanning, continuous adaptation of injection parameters to the acquisition speed seems to be necessary to avoid unneeded high amounts of contrast material on the one hand while still ensuring sufficient arterial enhancement on the other hand. The results of the present study underline the limited influence of high iodine concentration on diagnostic image quality and exemplify the still existing space for improvement in contrast injection protocols. Based on the results of the present study, the amount of contrast can be reduced by using ultrafast equipment without sacrificing image quality and/or diagnostic efficacy. Further studies would be of interest to evaluate the minimum amount of iodine needed for diagnostic abdominal MDCT angiograms. Finally, the excellent safety, robustness and reproducibility of abdominal MDCT angiography was shown in a clinical setting by the very small number of adverse events and very few examinations of limited quality. This underlines the outstanding role played by MDCT angiography in the diagnosis of diseases of the abdominal arteries.


Notes

This paper was presented as a scientific paper at ECR 2009.

This clinical trial was supported by Guerbet, Roissy, France.

Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.


References
1.. Glockner JF,Vrtiska TJ. Renal MR and CT angiography: current conceptsAbdom ImagingYear: 20073240742010.1007/s00261-006-9066-316952021
2.. Puchner S,Stadler A,Minar E,Lammer J,Bucek RA. Multidetector CT angiography in the follow-up of patients treated with renal artery stents: value of different reformation techniques compared with axial source imagesJ Endovasc TherYear: 20071438739410.1583/06-1970.117723005
3.. Saba L,Caddeo G,Sanfilippo R,Montisci R,Mallarini G. Multidetector-row CT angiography diagnostic sensitivity in evaluation of renal artery stenosis: comparison between multiple reconstruction techniquesJ Comput Assist TomogrYear: 20073171271610.1097/rct.0b013e31802fa90317895781
4.. Rau MM,Setty BN,Blake MA,Ouellette-Piazzo K,Hahn PF,Sahani DV. Evaluation of renal transplant donors with 16-section multidetector CT angiography: comparison of contrast media with low and high iodine concentrationsJ Vasc Interv RadiolYear: 20071860360910.1016/j.jvir.2007.02.01617494841
5.. Fleischmann D. Multiple detector-row CT angiography of the renal and mesenteric vesselsEur J RadiolYear: 200345S79S8710.1016/S0720-048X(02)00364-912598031
6.. Horton KM,Fishman EK. Multidetector CT angiography in the diagnosis of mesenteric ischemiaRadiol Clin North AmYear: 20074527528810.1016/j.rcl.2007.03.01017502217
7.. Willmann JK,Baumert B,Schertler T,Wildermuth S,Pfammatter T,Verdun FR,Seifert B,Marincek B,B?hm T. Aortoiliac and lower extremity arteries assessed with 16-detector row CT angiography: prospective comparison with digital subtraction angiographyRadiologyYear: 20052361083109310.1148/radiol.236204089516055691
8.. Yu T,Zhu X,Tang L,Wang D,Saad N. Review of CT angiography of aortaRadiol Clin North AmYear: 20074546148310.1016/j.rcl.2007.04.01017601503
9.. Teutelink A,Muhs BE,Vincken KL,Bartels LW,Cornelissen SA,Herwaarden JA,Prokop M,Moll FL,Verhagen HJ. Use of dynamic computed tomography to evaluate pre- and postoperative aortic changes in AAA patients undergoing endovascular aneurysm repairJ Endovasc TherYear: 200714444910.1583/06-1976.117291151
10.. Michaely HJ,Kramer H,Dietrich O,Nael K,Lodemann KP,Reiser MF,Schoenberg SO. Intraindividual comparison of high-spatial-resolution abdominal MR angiography at 1.5?T and 3.0?T: initial experienceRadiologyYear: 200724490791310.1148/radiol.244306164717709837
11.. Sutter R,Nanz D,Lutz AM,Pfammatter T,Seifert B,Struwe A,Heilmaier C,Weishaupt D,Marincek B,Willmann JK. Assessment of aortoiliac and renal arteries: MR angiography with parallel acquisition versus conventional MR angiography and digital subtraction angiographyRadiologyYear: 200724527628410.1148/radiol.245106208117717331
12.. Attenberger UI,Michaely HJ,Wintersperger BJ,Sourbron SP,Lodemann KP,Reiser MF,Schoenberg SO. Three-dimensional contrast-enhanced magnetic-resonance angiography of the renal arteries: interindividual comparison of 0.2?mmol/kg gadobutrol at 1.5?T and 0.1?mmol/kg gadobenate dimeglumine at 3.0?TEur RadiolYear: 2008181260126810.1007/s00330-008-0873-518278504
13.. Johnson PT,Fishman EK. IV contrast selection for MDCT: current thoughts and practiceAJR Am J RoentgenolYear: 200618640641510.2214/AJR.04.190216423946
14.. Katzberg RW,Barrett BJ. Risk of iodinated contrast material-induced nephropathy with intravenous administrationRadiologyYear: 200724362262810.1148/radiol.243306141117446526
15.. Thomsen HS,Morcos SK,Barrett BJ. Contrast-induced nephropathy: the wheel has turned 360 degreesActa RadiolYear: 20084964665710.1080/0284185080199541318568557
16.. Nyman U,Alm?n T,Aspelin P,Hellstr?m M,Kristiansson M,Sterner G. Contrast-medium-induced nephropathy correlated to the ratio between dose in gram iodine and estimated GFR in ml/minActa RadiolYear: 20054683084210.1080/0284185050033505116392608
17.. Fleischmann D,Rubin GD,Bankier AA,Hittmair K. Improved uniformity of aortic enhancement with customized contrast medium injection protocols at CT angiographyRadiologyYear: 200021436337110671582
18.. Hittmair K,Fleischmann D. Accuracy of predicting and controlling time-dependent aortic enhancement from a test bolus injectionJ Comput Assist TomogrYear: 20012528729410.1097/00004728-200103000-0002411242230
19.. Fleischmann D. How to design injection protocols for multiple detector-row CT angiography (MDCTA)Eur RadiolYear: 200515E60E6510.1007/s10406-005-0166-x18637231
20.. Behrendt FF,Mahnken AH,Keil S,Das M,Hohl C,Bauer D,Seidensticker P,Jost E,Wildberger JE,G?nther RW,M?hlenbruch G. Contrast enhancement in multidetector-row computed tomography (MDCT) of the abdomen: intraindividual comparison of contrast media containing 300?mg versus 370?mg iodine per mlEur RadiolYear: 2008181199120510.1007/s00330-008-0861-918228023
21.. Petersein J,Peters CR,Wolf M,Hamm B. Results of the safety and efficacy of iobitridol in more than 61,000 patientsEur RadiolYear: 2003132006201110.1007/s00330-002-1583-z12942302
22.. Valentini AL,Tartaglione T,Monti L,Marano P. Iomeprol versus iopamidol in contrast-enhanced computed tomography of thoracic and abdominal organsEur J RadiolYear: 199418S88S928020525
23.. Furuta A,Ito K,Fujita T,Koike S,Shimizu A,Matsunaga N. Hepatic enhancement in multiphasic contrast-enhanced MDCT: comparison of high- and low-iodine-concentration contrast medium in same patients with chronic liver diseaseAJR Am J RoentgenolYear: 200418315716215208131
24.. Awai K,Takada K,Onishi H,Hori S. Aortic and hepatic enhancement and tumor-to-liver contrast: analysis of the effect of different concentrations of contrast material at multi-detector row helical CTRadiologyYear: 200222475776310.1148/radiol.224301118812202710
25.. Suzuki H,Oshima H,Shiraki N,Ikeya C,Shibamoto Y. Comparison of two contrast materials with different iodine concentrations in enhancing the density of the aorta, portal vein and liver at multi-detector row CT: a randomized studyEur RadiolYear: 2004142099210410.1007/s00330-004-2439-515309493
26.. Bae KT,Heiken JP,Brink JA. Aortic and hepatic peak enhancement at CT: effect of contrast medium injection rate-pharmacokinetic analysis and experimental porcine modelRadiologyYear: 19982064554649457200
27.. Awai K,Inoue M,Yagyu Y,Watanabe M,Sano T,Nin S,Koike R,Nishimura Y,Yamashita Y. Moderate versus high concentration of contrast material for aortic and hepatic enhancement and tumor-to-liver contrast at multi-detector row CTRadiologyYear: 200423368268810.1148/radiol.233303161715486215
28.. Roos JE,Desbiolles LM,Weishaupt D,Wildermuth S,Hilfiker PR,Marincek B,Boehm T. Multi-detector row CT: effect of iodine dose reduction on hepatic and vascular enhancementRofoYear: 200417655656315088181
29.. Ho LM,Nelson RC,Thomas J,Gimenez EI,DeLong DM. Abdominal aortic aneurysms at multi-detector row helical CT: optimization with interactive determination of scanning delay and contrast medium doseRadiologyYear: 200423285485910.1148/radiol.232303100615333799

Figures

[Figure ID: Fig1]
Fig.?1a, b 

Principle of the measurement of arterial enhancement in the region of the suprarenal aorta, demonstrated in a patient examined with administration of 100?ml iobitridol because of infrarenal aortic aneurysm. Region of interest (ROI) is defined at the same table position in the baseline examination (a) as well as in the arterial phase images (b), as round surfaces in the lumen of the vessel, the circumference of which should not extend beyond the internal limit of the arterial wall



[Figure ID: Fig2]
Fig.?2 

Two examples of abdominal aortic angiograms (maximum intensity projections, MIP) obtained during the administration of two contrast agents. The patient in a was examined during administration of 100?ml iobitridol 350?mgI/ml, and the patient in b received 100?ml iomeprol 400?mgI/ml. Regardless of the different total amounts of iodine, both MIPs show excellent and homogeneous arterial enhancement without visualised differences



Tables
[TableWrap ID: Tab1] Table?1 

Demographic data of the study population


? Iobitridol 350 (n?=?154) Iomeprol 400 (n?=?156) All (n?=?310)
Sex
Male 115 (74.7%) 132 (84.6%) 247 (79.7%)
Female 39 (25.3%) 24 (15.4%) 63 (20.3%)
Age (years)
n 154 156 310
Mean (SD) 65.2 (10.9) 67.8 (9.8) 66.5 (10.4)
Median 66.0 69.0 68.0
Min/max 30.0 90.0 35.0 86.0 30.0 90.0
Height (cm)
n 154 156 310
Mean (SD) 172.4 (8.8) 172.1 (8.1) 172.2 (8.5)
Median 172.5 172.0 172.0
Min/max 150 196 152 193 150 196
Weight (kg)
n 154 156 310
Mean (SD) 78.5 (16.1) 79.4 (15.7) 78.9 (15.9)
Median 79.0 78.5 79.0
Min/max 44.0 122.0 41.0 130.0 41.0 130.0
Body mass index (kg/m2)
n 154 156 310
Mean (SD) 26.3 (4.3) 26.7 (4.5) 26.5 (4.4)
Median 26.4 26.0 26.1
Min/max 17.6 39.4 16.7 40.5 16.7 40.5

[TableWrap ID: Tab2] Table?2 

Injection protocols by centre and overall


Centre (n patients) Volume (ml) Iodine (g) Flow rate (ml/s)
Mean Min Max Mean Min Max Mean Min Max
Centre 1
Total (39) 100 100 100 37.4 35 40 5.0 4.0 5.0
Iobitridol (20) 100 100 100 35 35 35 5.0 4.0 5.0
Iomeprol (19) 100 100 100 40 40 40 5.0 5.0 5.0
Centre 2
Total (40) 120 120 120 45 42 48 3.0 3.0 3.0
Iobitridol (20) 120 120 120 42 42 42 3.0 3.0 3.0
Iomeprol (20) 120 120 120 48 48 48 3.0 3.0 3.0
Centre 4
Total (35) 90 90 90 33.8 31.5 36 3.5 3.5 3.5
Iobitridol (17) 90 90 90 31.5 31.5 31.5 3.5 3.5 3.5
Iomeprol (18) 90 90 90 36 36 36 3.5 3.5 3.5
Centre 7
Total (35) 100 100 100 37.6 35 40 3.0 3.0 3.0
Iobitridol (17) 100 100 100 35 35 35 3.0 3.0 3.0
Iomeprol (18) 100 100 100 40 40 40 3.0 3.0 3.0
Centre 3
Total (38) 89.7 80 140 33.7 28 56 4.8 2.5 5.3
Iobitridol (19) 88.9 80 90 31.1 28 31.5 4.9 4.0 5.2
Iomeprol (19) 90.5 80 140 36.2 32 56 4.6 2.5 5.3
Centre 5
Total (27) 117.8 100 120 44.1 35 48 4.0 4.0 4.0
Iobitridol (14) 117.1 100 120 41 35 42 4.0 4.0 4.0
Iomeprol (13) 118.5 100 120 47.4 40 48 4.0 4.0 4.0
Centre 6
Total (30) 115.4 63 120 43.4 25.2 48 5.0 5.0 5.0
Iobitridol (14) 117.1 100 120 41 35 42 5.0 5.0 5.0
Iomeprol (16) 113.9 63 120 45.6 25.2 48 5.0 5.0 5.0
Centre 8
Total (26) 110.4 74 135 41.4 28 51.2 5.5 4.5 6.0
Iobitridol (13) 110.8 80 135 38.8 28 47.3 5.4 4.5 6.0
Iomeprol (13) 109.9 74 128 44 29.6 51.2 5.5 5.0 6.0
Centre 9
Total (39) 77.4 70 140 29 24.5 56 4.0 4.0 4.2
Iobitridol (20) 76 70 140 26.6 24.5 49 4.0 4.0 4.2
Iomeprol (19) 78.9 70 140 31.6 28 56 4.0 4.0 4.0
Total
Total (309) 101.3 63 140 38 24.5 56 4.1 2.5 6.0
Iobitridol (154) 101 70 140 35.4 24.5 49 4.2 3.0 6.0
Iomeprol (155) 101.5 63 140 40.6 25.2 56 4.1 2.5 6.0

Centres 1, 2, 4 and 7: constant volumes regardless of patients? weight, conditions or indication of examination

Centres 3, 5, 6, 8 and 9: volumes adjusted based on patients? weight, conditions or indication of examination


[TableWrap ID: Tab3] Table?3 

Diagnostic efficacy according to patients


Injected product All Statistical test
Iobitridol 350 (n?=?153) Iomeprol 400 (n?=?154) (n?=?307)
n % n % n %
MDCT diagnostic efficacy
Not satisfactory/not providing enough information 0 0.0% 1 0.6% 1 0.3%
Not satisfactory/not providing all expected information 1 0.7% 0 0.0% 1 0.3%
Satisfactory/providing sufficient information 3 2.0% 2 1.3% 5 1.6%
Totally satisfactory/providing expected information 149 97.4% 151 98.1% 300 97.7%
MDCT diagnostic efficacy, primary endpoint
Not satisfactory 1 0.7% 1 0.6% 2 0.7% Asympt. 95% CI: [?1.8%; 1.8%]
Totally satisfactory/satisfactory 152 99.3% 153 99.4% 305 99.3% Exact 95% CI: [?2.98%; 3.01%], P?=?0.00002a
MDCT diagnostic efficacy, totally satisfactory
Not totally satisfactory 4 2.6% 3 1.9% 7 2.3% Asympt. 95% CI: [?4.01%; 2.67%]
Totally satisfactory 149 97.4% 151 98.1% 300 97.7% Exact 95% CI: [?4.82%; 3.23%], P?=?0.0002a

Generalised linear model: y = intercept + product

aExact statistical P value for main effect (difference between products ? 10%)


[TableWrap ID: Tab4] Table?4 

Image quality assessments in vessel segments


? Injected product All Statistical test
Iobitridol 350 (n?=?2,448) Iomeprol 400 (n?=?2,464) (n?=?4,912)
n % n % n %
Image quality in vessels
? 1 0 1
NA (out of the FOV) 32 1.3% 50 2.0% 82 1.7%
Null 64 2.6% 52 2.1% 116 2.4%
Poor 32 1.3% 26 1.1% 58 1.2%
Good 168 6.9% 146 5.9% 314 6.4%
Excellent 2,151 87.9% 2,190 88.9% 4,341 88.4%
Image quality in vessels, good/excellent
?/NA 33 50 83 Asympt. 95% CI: [?3.30%; 1.84%]
Null/poor 96 3.9% 78 3.2% 174 3.5% P?=?0.5769a
Good/excellent 2,319 94.7% 2,336 94.8% 4,655 94.8% P?=?0.3011b
Image quality in vessels, score
Vessel segments (n) 2,415 2,414 4,829
Mean (SD) 2.824 (0.57) 2.853 (0.53) 2.839 (0.55) Asympt. 95% CI: [?0.109; 0.051]
Median 3.0 3.0 3.0 P?=?0.4755a
Min/max 0/3 0/3 0/3 P?=?0.3103b

Generalised linear model: y = intercept + product + segment + product ? segment (clustered within subjects)

aWald stat. P value for main effect (difference between products ? 0)

bWald stat. P value for interaction (difference between products changes with segments)


[TableWrap ID: Tab5] Table?5 

Image quality assessments in vascular wall segments


? Injected product All Statistical test
Iobitridol 350 (n?=?2,448) Iomeprol 400 (n?=?2,464) (n?=?4,912)
n % n % n %
Image quality in vascular walls
? 2 0 2
NA (out of the FOV) 32 1.3% 50 2.0% 82 1.7%
Null 77 3.1% 65 2.6% 142 2.9%
Poor 273 11.2% 300 12.2% 573 11.7%
Good 222 9.1% 282 11.4% 504 10.3%
Excellent 1842 75.2% 1767 71.7% 3609 73.5%
Image quality in vascular walls, good/excellent
?/ NA 34 50 84 Asympt. 95% CI: [?6.33%, 7.87%]
Null/poor 350 14.3% 365 14.8% 715 14.6% P?=?0.8316a
Good/excellent 2,064 84.3% 2,049 83.2% 4,113 83.7% P?=?0.1286b
Image quality in vascular walls, score
Vascular wall segments (n) 2,414 2,414 4,828 Asympt. 95% CI: [?0.118; 0.181]
Mean (SD) 2.586 (0.81) 2.554 (0.81) 2.570 (0.81)
Median 3.0 3.0 3.0 P?=?0.6789a
Min/max 0/3 0/3 0/3 P?=?0.3911b

Generalised linear model: y = intercept + product + segment + product ? segment (clustered within subjects)

aWald stat. P value for main effect (difference between products ? 0)

bWald stat. P value for interaction (difference between products changes with segments)


[TableWrap ID: Tab6] Table?6 

Quantification of MDCT enhancement, attenuation variation


? Injected product All Statistical tests
Iobitridol 350 (n?=?1,224) Iomeprol 400 (n?=?1,232) (n?=?2,456)
Baseline attenuation (HU)
n 1,162 1,153 2,315
Mean (SD) 40.0 (12.14) 40.8 (12.49) 40.4 (12.32)
Median 40.0 41.0 41.0
Min/max 3/90 3/94 3/94
Post-contrast attenuation (HU)
n 1,196 1,197 2,393
Mean (SD) 320.4 (93.54) 353.6 (95.45) 337.0 (95.93)
Median 306.0 349.0 327.0
Min/max 42/638 25/770 25/770
Attenuation absolute variations from baseline (HU)
n 1,160 1,152 2,312
Mean (SD) 282.3 (93.59) 314.0 (96.20) 298.0 (96.19) Asympt. 95% CI: [?53.47; ?12.85]
Median 271.0 309.0 289.0 P?=?0.0014a
Min/max ?4/588 ?12/745 ?12/745 P?=?0.7017b
Attenuation relative variations from baseline
n 1160 1152 2312
Mean (SD) 8.123 (5.9357) 8.863 (5.4576) 8.492 (5.7132) Asympt. 95% CI: [?1.53; 0.053]
Median 7.043 7.817 7.403 P?=?0.0673a
Min/max ?0.06/129.00 ?0.26/65.83 ?0.26/129.00 P?=?0.6205b

n Number of vessel segments

Generalised linear model: y = intercept + product + segment + product ? segment (clustered within subjects)

aWald stat. P value for main effect (difference between products ? 0)

bWald stat. P value for interaction (difference between products changes with segments)



Article Categories:
  • Computed Tomography

Keywords: Keywords CT angiography, Abdominal arterial tree, Diagnostic efficacy, Iodinated contrast agents.

Previous Document:  Sensitivity and reliability of language laterality assessment with a free reversed association task-...
Next Document:  Do the cardiovascular risk profile and the degree of arterial wall calcification influence the perfo...